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Respiration-correlated spiral CT: a method of measuring respiratory-induced anatomic motion for radiation treatment planning.

We describe a method for generating CT images at multiple respiratory phases with a single spiral CT scan, referred to as respiratory-correlated spiral CT (RCCT). RCCT relies on a respiration wave form supplied by an external patient monitor. During acquisition this wave form is recorded along with the initiation time of the CT scan, so as to "time stamp" each reconstructed slice with the phase of the respiratory cycle. By selecting the appropriate slices, a full CT image set is generated at several phases, typically 7-11 per cycle. The CT parameters are chosen to optimize the temporal resolution while minimizing the spatial gap between slices at successive respiratory cycles. Using a pitch of 0.5, a gantry rotation period of 1.5 s, and a 180 degrees reconstruction algorithm results in approximately 5 mm slice spacing at a given phase for typical respiration periods, and a respiratory motion within each slice that is acceptably small, particularly near end expiration or end inspiration where gated radiotherapy is to occur. We have performed validation measurements on a phantom with a moving sphere designed to simulate respiration-induced tumor motion. RCCT scans of the phantom at respiratory periods of 4, 5, and 6 s show good agreement of the sphere's motion with that observed under fluoroscopic imaging. The positional deviations in the sphere's centroid between RCCT and fluoroscopy are 1.1+/-0.9 mm in the transaxial direction (average over all scans at all phases +/-1 s.d.) and 1.2+/-1.0 mm in the longitudinal direction. Reconstructed volumes match those expected on the basis of stationary-phantom scans to within 5% in all cases. The surface distortions of the reconstructed sphere, as quantified by deviations from a mathematical reference sphere, are similar to those from a stationary phantom scan and are correlated with the speed of the phantom. A RCCT scan of the phantom undergoing irregular motion, demonstrates that successful reconstruction can be achieved even with irregular respiration. Limitations from x-ray tube heating in our current CT unit restrict the length of the scan region to 9 cm for the RCCT settings used, though this will not be a limitation for a multislice scanner. RCCT offers an alternative to the current method of respiration-triggered axial scans. Multiple phases of respiration are imaged with RCCT in approximately the same scanning time required to image a single phase with a triggered axial scan. RCCT scans can be used in connection with respiratory-gated treatment to identify the patient-specific phase of minimum tumor motion, determine residual tumor motion within the gate interval, and compare treatment plans at different phases.

Artifacts↗

Ionization chamber volume averaging effects in dynamic intensity modulated radiation therapy beams.

The commercial cylindrical ionization chamber ionization integration accuracy of dynamically moving fields was evaluated. The ionization chambers were exposed to long (14 cm), narrow (0.6, 1.0, 2.0, and 4.0 cm) 6 MV and 18 MV fields. Rather than rely on the linear accelerator to reproducibly scan across the chamber, the chambers were scanned beneath fixed portals. A water-equivalent phantom was constructed with cavities that matched the chambers and placed on a computer-controlled one-dimensional table. Computer-controlled electrometers were utilized in continuous charge integrate mode, with 10 samples of the charge, along with time stamps, acquired for each chamber location. A reference chamber was placed just beneath the linear accelerator jaws to adjust for variations in linear accelerator dose rate. The scan spatial resolution was selected to adequately sample regions of steep dose gradient and second spatial derivative (curvature). A fixed measurement in a 10 x 10 cm2 field was used to normalize the profiles to absolute chamber response. Three ionization chambers were tested, a microchamber (0.009 cm3), a Farmer chamber (0.6 cm3) and a waterproof scanning chamber (0.125 cm3). The larger chambers exhibited severe under-response at the small field's centers, but all of the chambers, independent of orientation, accurately integrated the ionization across the scanned portal. This indicates that the tested ionization chambers provide accurate integrated charges in regions of homogeneous dose regions. Partial integration (less than the field width plus the chamber length plus 2 cm), yielded integration errors of greater than 1% and 2% for 6 MV and 18 MV, respectively, with errors for the Farmer chamber of greater than 10% even for the 4 cm wide field.

Equipment Failure Analysis↗

Four-dimensional (4D) PET/CT imaging of the thorax.

We have reported in our previous studies on the methodology, and feasibility of 4D-PET (Gated PET) acquisition, to reduce respiratory motion artifact in PET imaging of the thorax. In this study, we expand our investigation to address the problem of respiration motion in PET/CT imaging. The respiratory motion of four lung cancer patients were monitored by tracking external markers placed on the thorax. A 4D-CT acquisition was performed using a "step-and-shoot" technique, in which computed tomography (CT) projection data were acquired over a complete respiratory cycle at each couch position. The period of each CT acquisition segment was time stamped with an "x-ray ON" signal, which was recorded by the tracking system. 4D-CT data were then sorted into 10 groups, according to their corresponding phase of the breathing cycle. 4D-PET data were acquired in the gated mode, where each breathing cycle was divided into ten 0.5 s bins. For both CT and PET acquisitions, patients received audio prompting to regularize breathing. The 4D-CT and 4D-PET data were then correlated according to respiratory phase. The effect of 4D acquisition on improving the co-registration of PET and CT images, reducing motion smearing, and consequently increase the quantitation of the SUV, were investigated. Also, quantitation of the tumor motions in PET, and CT, were studied and compared. 4D-PET with matching phase 4D-CTAC showed an improved accuracy in PET-CT image co-registration of up to 41%, compared to measurements from 4D-PET with clinical-CTAC. Gating PET data in correlation with respiratory motion reduced motion-induced smearing, thereby decreasing the observed tumor volume, by as much as 43%. 4D-PET lesions volumes showed a maximum deviation of 19% between clinical CT and phase- matched 4D-CT attenuation corrected PET images. In CT, 4D acquisition resulted in increasing the tumor volume in two patients by up to 79%, and decreasing it in the other two by up to 35%. Consequently, these corrections have yielded an increase in the measured SUV by up to 16% over the clinical measured SUV, and 36% over SUV's measured in 4D-PET with clinical-CT Attenuation Correction (CTAC) SUV's. Quantitation of the maximum tumor motion amplitude, using 4D-PET and 4D-CT, showed up to 30% discrepancy between the two modalities. We have shown that 4D PET/CT is clinically a feasible method, to correct for respiratory motion artifacts in PET/CT imaging of the thorax. 4D PET/CT acquisition can reduce smearing, improve the accuracy in PET-CT co-registration, and increase the measured SUV. This should result in an improved tumor assessment for patients with lung malignancies.

Aged↗

Vivo motion and force measurement of surgical needle intervention during prostate brachytherapy.

In this paper, we present needle insertion forces and motion trajectories measured during actual brachytherapy needle insertion while implanting radioactive seeds in the prostate glands of 20 different patients. The needle motion was captured using ultrasound images and a 6 degree-of-freedom electromagnetic-based position sensor. Needle velocity was computed from the position information and the corresponding time stamps. From in vivo data we found the maximum needle insertion forces to be about 15.6 and 8.9 N for 17 gauge (1.47 mm) and 18 gauge (1.27 mm) needles, respectively. Part of this difference in insertion forces is due to the needle size difference (17G and 18G) and the other part is due to the difference in tissue properties that are specific to the individual patient. Some transverse forces were observed, which are attributed to several factors such as tissue heterogeneity, organ movement, human factors in surgery, and the interaction between the template and the needle. However, theses insertion forces are significantly responsible for needle deviation from the desired trajectory and target movement. Therefore, a proper selection of needle and modulated velocity (translational and rotational) may reduce the tissue deformation and target movement by reducing insertion forces and thereby improve the seed delivery accuracy. The knowledge gleaned from this study promises to be useful for not only designing mechanical/robotic systems but also developing a predictive deformation model of the prostate and real-time adaptive controlling of the needle.

Brachytherapy↗

Ultrasound fields in attenuating media.

For medical ultrasonic imaging and for nondestructive testing, the attenuation of pressure waves and the resulting shift in wave velocity are important features in commonly used transmission media such as biological tissue. An algorithm for the numerical evaluation of pressure field distributions generated by ultrasonic transducers is presented. The attenuation and dispersion of the sound transmission medium are taken into consideration. The sound fields are computed numerically for continuous wave as well as pulse excitation. The transducer has plane or gently curved geometry and is embedded in a plane rigid baffle. The numerically determined pressure fields are presented as 3D plots, as gray-scale images for a fixed time stamp (like a snapshot), or as isobars regarding the maximum values over time for each local point in the area under investigation. The algorithm described here can be utilized as a tool for design of ultrasound transducers, especially array antennas.

Algorithms↗

Submicrometer patterning of charge in thin-film electrets.

Thin-film electrets have been patterned with trapped charge with submicrometer resolution using a flexible, electrically conductive electrode. A poly(dimethylsiloxane) stamp, patterned in bas-relief and supporting an 80-nanometer-thick gold film, is brought into contact with an 80-nanometer-thick film of poly(methylmethacrylate) supported on n-doped silicon. A voltage pulse between the gold film and the silicon transfers charge at the contact areas between the gold and the polymer electret. Areas as large as 1 square centimeter were patterned with trapped charges at a resolution better than 150 nanometers in less than 20 seconds. This process provides a new method for patterning; it suggests possible methods for high-density, charge-based data storage and for high-resolution charge-based printing.

Journal Article↗

Empirical analysis of an evolving social network.

Social networks evolve over time, driven by the shared activities and affiliations of their members, by similarity of individuals' attributes, and by the closure of short network cycles. We analyzed a dynamic social network comprising 43,553 students, faculty, and staff at a large university, in which interactions between individuals are inferred from time-stamped e-mail headers recorded over one academic year and are matched with affiliations and attributes. We found that network evolution is dominated by a combination of effects arising from network topology itself and the organizational structure in which the network is embedded. In the absence of global perturbations, average network properties appear to approach an equilibrium state, whereas individual properties are unstable.

Electronic Mail↗

Heterogeneous three-dimensional electronics by use of printed semiconductor nanomaterials.

We developed a simple approach to combine broad classes of dissimilar materials into heterogeneously integrated electronic systems with two- or three-dimensional layouts. The process begins with the synthesis of different semiconductor nanomaterials, such as single-walled carbon nanotubes and single-crystal micro- and nanoscale wires and ribbons of gallium nitride, silicon, and gallium arsenide on separate substrates. Repeated application of an additive, transfer printing process that uses soft stamps with these substrates as donors, followed by device and interconnect formation, yields high-performance heterogeneously integrated electronics that incorporate any combination of semiconductor nanomaterials on rigid or flexible device substrates. This versatile methodology can produce a wide range of unusual electronic systems that would be impossible to achieve with other techniques.

Journal Article↗

Population biology of antigen presentation by MHC class I molecules.

In principle, the function of major histocompatibility complex (MHC) molecules is simple: to bind a peptide and engage a T cell. In practice, placing this function within the context of the immune response begs questions of population biology; How does the immune response emerge from the interactions among populations of peptides, T cells and MHC molecules? Within a population of vertebrates, how does MHC polymorphism stamp individuality on the response? Does polymorphism confer differential advantages in responding to parasites? How are the pressures on the MHC reflected in turnover of alleles? The role of mutation, recombination, selection, and drift in the generation and maintenance of MHC class 1 polymorphism are considered.

Amino Acid Sequence↗

Monolithic microfabricated valves and pumps by multilayer soft lithography.

Soft lithography is an alternative to silicon-based micromachining that uses replica molding of nontraditional elastomeric materials to fabricate stamps and microfluidic channels. We describe here an extension to the soft lithography paradigm, multilayer soft lithography, with which devices consisting of multiple layers may be fabricated from soft materials. We used this technique to build active microfluidic systems containing on-off valves, switching valves, and pumps entirely out of elastomer. The softness of these materials allows the device areas to be reduced by more than two orders of magnitude compared with silicon-based devices. The other advantages of soft lithography, such as rapid prototyping, ease of fabrication, and biocompatibility, are retained.

Adhesiveness↗

Engineering cell shape and function.

An elastomeric stamp, containing defined features on the micrometer scale, was used to imprint gold surfaces with specific patterns of self-assembled monolayers of alkanethiols and, thereby, to create islands of defined shape and size that support extracellular matrix protein adsorption and cell attachment. Through this technique, it was possible to place cells in predetermined locations and arrays, separated by defined distances, and to dictate their shape. Limiting the degree of cell extension provided control over cell growth and protein secretion. This method is experimentally simple and highly adaptable. It should be useful for applications in biotechnology that require analysis of individual cells cultured at high density or repeated access to cells placed in specified locations.

Albumins↗

Fourier-transform infrared microspectroscopy, a novel and rapid tool for identification of yeasts.

Fourier-transform infrared (FT-IR) microspectroscopy was used in this study to identify yeasts. Cells were grown to microcolonies of 70 to 250 micro m in diameter and transferred from the agar plate by replica stamping to an IR-transparent ZnSe carrier. IR spectra of the replicas on the carrier were recorded using an IR microscope coupled to an IR spectrometer, and identification was performed by comparison to reference spectra. The method was tested by using small model libraries comprising reference spectra of 45 strains from 9 genera and 13 species, recorded with both FT-IR microspectroscopy and FT-IR macrospectroscopy. The results show that identification by FT-IR microspectroscopy is equivalent to that achieved by FT-IR macrospectroscopy but the time-consuming isolation of the organisms prior to identification is not necessary. Therefore, this method also provides a rapid tool to analyze mixed populations. Furthermore, identification of 21 Debaryomyces hansenii and 9 Saccharomyces cerevisiae strains resulted in 92% correct identification at the strain level for S. cerevisiae and 91% for D. hansenii, which demonstrates that the resolution power of FT-IR microspectroscopy may also be used for yeast typing at the strain level.

Microbiological Techniques↗

Improved methodology for isolating soil microorganisms.

Polyurethane foam cylinders and a replica-stamp technique were used for plating soil samples. This in conjunction with the addition of NaCl to the isolation medium substantially increased the variety of isolates recovered.

Journal Article↗

Rapid method for determining serum bactericidal activity.

To screen large numbers of sera, a method was devised which utilizes the Steers-Foltz replicator which is usually used to determine minimal inhibitory concentration for antibiotics. Each of the wells (9 by 15 mm) of the replicator is filled with 0.06 ml of serum, 0.02 ml of a 10(5) suspension of organisms, and 0.02 ml of diluent (tris(hydroxymethyl)aminomethane-hydrochloride buffer, pH 8.4). The mixtures are incubated for 3 h, and samples are taken at 0, 1, 2, and 3 h by stamping duplicate nutrient agar plates (approximately 0.04 ml from each well). Plates are incubated overnight, and bactericidal activity is estimated by visual inspection of bacterial growth at each site for each sampling time. Results obtained with 28 serum-organism pairs paralleled standard pipetting-pour plate methods. The replicator method for determining bactericidal activity allows for the testing of a large number of samples and requires negligible amounts of serum.

Blood Bactericidal Activity↗

Isolation of Coxiella burnetii from heart valves of patients treated for Q fever endocarditis.

Coxiella burnetii was isolated from the valve material of two patients who underwent valvectomy because of progressive congestive heart failure due to endocarditis. In each case antibiotic therapy was administered for several months prior to valvectomy. Classical histopathological examination of the valves did not reveal an etiology. However, coxiella-like organisms were demonstrated in valvular material with Köster, Stamp, and Giemsa stains, and the organisms were grown in cell culture. Antibody titers were consistent with the diagnosis of chronic C. burnetii infection. This report illustrates the advantage of simple and fast staining techniques and cell culture for the demonstration and isolation of C. burnetii in the heart valve tissue of patients with Q fever endocarditis.

Antibodies, Bacterial↗

Control of pain in the rheumatic disorders.

Pain may be attacked in the rheumatic diseases (1) centrally, with drugs ranging in efficiency from those which are potentially addictive and under the Dangerous Drugs Act (e.g., pethidine) and are therefore rarely used, down to simple analgesics such as paracetamol; (2) peripherally, by local action, whether it be by applications of heat or cold, by injections of local anaesthetics or anti-inflammatory agents, or by surgery; (3) peripherally, by anti-inflammatory non-analgesic agents taken systemically, such as the corticosteroids; and (4) peripherally, by anti-inflammatory-analgesic-antipyretic agents taken systemically, such as aspirin.The exact sites of action of the pyrazoles, indomethacin, the anthranilic compounds, and other anti-inflammatory-analgesic-antipyretic drugs are as yet uncertain, but along with these methods of attacking the pain-producing areas help must also be given to the distressed mind behind the joints. Faith in the future, cheerfulness, freedom from depression, and the development of a philosophy to deal with the uncertainties of the disease are essential. It has been said that you don't have to be a doctor to treat uncomplicated lobar pneumonia: anybody with a bottle of penicillin in his hands holds the cure. It is the incurable diseases that are really worth treating, and that make demands on the physician. To quote Tuker: "My last word is this. Whoever has the care of a sorely stricken arthritic must encourage him to fulfil himself intellectually and spiritually, and to achieve-no matter what, but to achieve, so that he may nightly lay himself down on his bed of pain looking forward happily to the morrow's task, mind centred upon it, no matter what it is; sticking in stamps, research into anything you like, dabbling with pastel or water colours, writing chatty letters to friends. Anything at all, but let it be for him the most pressing thing of the day, and let him believe that you think it is. Help him and let him live, live fully."This is perhaps the best analgesic of all.

Analgesics↗

Inequality in income and mortality in the United States: analysis of mortality and potential pathways.

OBJECTIVE: To examine the relation between health outcomes and the equality with which income is distributed in the United States. DESIGN: The degree of income inequality, defined as the percentage of total household income received by the less well off 50% of households, and changes in income inequality were calculated for the 50 states in 1980 and 1990. These measures were then examined in relation to all cause mortality adjusted for age for each state, age specific deaths, changes in mortalities, and other health outcomes and potential pathways for 1980, 1990, and 1989-91. MAIN OUTCOME MEASURE: Age adjusted mortality from all causes. RESULTS: There was a significant correlation (r = -0.62 [corrected], P < 0.001) between the percentage of total household income received by the less well off 50% in each state and all cause mortality, unaffected by adjustment for state median incomes. Income inequality was also significantly associated with age specific mortalities and rates of low birth weight, homicide, violent crime, work disability, expenditures on medical care and police protection, smoking, and sedentary activity. Rates of unemployment, imprisonment, recipients of income assistance and food stamps, lack of medical insurance, and educational outcomes were also worse as income inequality increased. Income inequality was also associated with mortality trends, and there was a suggestion of an impact of inequality trends on mortality trends. CONCLUSION: Variations between states in the inequality of the distribution of income are significantly associated with variations between states in a large number of health outcomes and social indicators and with mortality trends. These differences parallel relative investments in human and social capital. Economic policies that influence income and wealth inequality may have an important impact on the health of countries.

Adolescent↗

Increasing response rates to postal questionnaires: systematic review.

OBJECTIVE: To identify methods to increase response to postal questionnaires. DESIGN: Systematic review of randomised controlled trials of any method to influence response to postal questionnaires. STUDIES REVIEWED: 292 randomised controlled trials including 258 315 participants INTERVENTION REVIEWED: 75 strategies for influencing response to postal questionnaires. MAIN OUTCOME MEASURE: The proportion of completed or partially completed questionnaires returned. RESULTS: The odds of response were more than doubled when a monetary incentive was used (odds ratio 2.02; 95% confidence interval 1.79 to 2.27) and almost doubled when incentives were not conditional on response (1.71; 1.29 to 2.26). Response was more likely when short questionnaires were used (1.86; 1.55 to 2.24). Personalised questionnaires and letters increased response (1.16; 1.06 to 1.28), as did the use of coloured ink (1.39; 1.16 to 1.67). The odds of response were more than doubled when the questionnaires were sent by recorded delivery (2.21; 1.51 to 3.25) and increased when stamped return envelopes were used (1.26; 1.13 to 1.41) and questionnaires were sent by first class post (1.12; 1.02 to 1.23). Contacting participants before sending questionnaires increased response (1.54; 1.24 to 1.92), as did follow up contact (1.44; 1.22 to 1.70) and providing non-respondents with a second copy of the questionnaire (1.41; 1.02 to 1.94). Questionnaires designed to be of more interest to participants were more likely to be returned (2.44; 1.99 to 3.01), but questionnaires containing questions of a sensitive nature were less likely to be returned (0.92; 0.87 to 0.98). Questionnaires originating from universities were more likely to be returned than were questionnaires from other sources, such as commercial organisations (1.31; 1.11 to 1.54). CONCLUSIONS: Health researchers using postal questionnaires can improve the quality of their research by using the strategies shown to be effective in this systematic review.

Data Collection↗